Reactive immunization provides a unique opportunity to generate catalytic antibodies that are efficient yet broad in scope (Shultz, P. G., et al., Science 1995, 269, 1835; Keinan, E., et al. Israel J. Chem. 1996, 36, 113; and Reymond, J.-L. Top. Curr. Chem. 1999, 200, 59). Recently, two aldolase antibodies 33F12 and 38C2 were generated against a .beta.-diketone hapten, 6-(4-glutaramidophenyl)-hexane-2,4-dione, using reactive immunization (Wagner, J., et al., Science 1995, 270, 1797). These antibody catalysts were found to be useful synthetic catalysts in that they catalyze a wide range of aldol- and retro-aldol reactions, typically with a very high degree of enantioselectivity (Zhong, G., et al., J. Am. Chem. Soc. 1997, 119, 8131; List, B., et al., Chem. Eur. J. 1998, 4, 881; Hoffmann, T., et al., J. Am. Chem. Soc. 1998, 120, 2768; Barbas, C. F, et al., Science 1998, 278, 2085; Zhong, G., et al. Angew. Chem. Int. Ed. Engl. 1998, 37, 2481; and List, B., et al., J. Am. Chem. Soc. 1999, 121, 7283).
Epothilones A-E, 2-6, are sixteen-membered macrolides isolated from myxobacteria, i.e., Sorangium cellulosum strain 90 (Bollag, D. M., et al., Cancer Res. 1995, 55, 2325; Gerth, K., et al., J. Antibiot. 1996, 49, 560; Hofle, G., et al., Angew. Chem. Int. Ed. Engl. 1996, 35, 1567; and Nicolaou, K. C., et al., Angew. Chem. Int. Ed. Engl. 1998, 37, 2014). Several total syntheses of epothilones A-E as well as their analogs have been achieved. For the first total syntheses of epothilones A-D, see: (a) Balog, A., et al., Angew. Chem. Int. Ed. Engl. 1996, 35, 2801; Su, D.-S., et al., Angew. Chem. Int. Ed. Eng. 1997, 36, 757. Syntheses of epothilones A and C were simultaneously reported by Nicolaou and Schinzer groups (Schinzer, D., et al., Angew. Chem. Int. Ed. Engl. 1997, 36, 523; and Nicolaou, K. C., et al., Angew. Chem. Int. Ed. Eng. 1997, 36, 525). For the synthesis of epothilone E, see: Nicolaou, K. C., et al., Angew. Chem. Int. Edn. Eng. 1998, 37, 84. For the recent total synthesis of other epothilones see: May, S. A., et al., Chem. Commun. 1998, 1597; Mulzer, J., et al. Tetrahedron Lett. 1998, 39, 8633; Harris, C. R., et al. Tetrahedron Lett. 1999, 40, 2263; Nicolaou, K. C., et al., Chem. Commun. 1999, 519; Nicolaou, K. C., et al., Bioorg. Med. Chem. 1999, 7, 665; and White, J. D., et al., J. Org. Chem. 1999, 64, 684. The biological properties of epothilones A-E and their analogs have also been recorded (Chou, T.-C., et al., Proc. Natl. Acad. Sci. USA 1998, 95, 9642 and references cited therein). Recently, a synthesis of the naturally occurring epothilones A-D, 2 and 4, starting from aldol products obtained either by an antibody 38C2-catalyzed aldol addition of acetone to the aldehyde 10 or by an enantioselective resolution of a racemic aldol product using antibody 38C2 (Sinha, S. C., et al., Proc. Natl. Acad. Sci. USA 1998, 95, 14603).